Plans for the fifth year of funding involve four general research areas: 1 The development and improvement of standardized methods for the tracer kinetic study of brain function, 2. Standardization of anatomical approaches to functional image analysis. 3. The evaluation of normal subjects in resting states and during specific sensory, motor and cognitive tasks and 4. The continued evaluation and collaboration with other investigators in the study of patients with Huntington's Disease, Aphasia, Epilepsy, Affective Disorders and Dementia. In the area of methodological development, I will continue the human and animal experimentation needed to validate the bolus approach to oxygen utilization studies. In the realm of anatomical standardization, I will complete a series of NIMH sponsored workshops for the standardization and identification of regions from functional images obtained with PET and SPECT. In our own laboratory these approaches will be implemented and a laboratory wide data base will be established for the integrated exchange of data between experimental protocols in both animals and humans. Studies in normal subjects with PET will include the use of oxygen-15 labeled compounds and FDG for our new tomograph. These studies will provide new values for kinetic rate constants of the deoxyglucose model and initial high resolution values for the human brain for cerebral glucose metabolism, blood flow, blood volume, oxygen utilization and oxygen extraction fraction. Continued studies of the motor system will expand our original approach in normal subjects to evaluate tasks in patients with motor system diseases including Huntington's Disease, Wilson's Disease, Tardive Dyskinesia and Parkinson's Disease. Other patient studies will include the continuation of our work in Huntington's Disease with emphasis on correlating our studies in at risk patients with genetic linkage studies performed for the identification of the Huntington's Disease gene. Expansion of our work in patients with affective disorders will include provocative stimuli from both behavioral tasks and pharmacological manipulations with antidepressant drugs and stimulants.